amikacin and cefepime

Action and Spectrum

Actions and spectrum: 

amikacin: 

• Action: amikacin is an aminoglycoside antibiotic that works by inhibiting protein synthesis in bacteria. It does this by binding to the bacterial ribosomes, which are essential for protein production, leading to bacterial cell death. 
• Spectrum: amikacin is effective against a broad range of Gram-negative bacteria, that are resistant to other antibiotics. It is often used to treat serious infections like those caused by Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae. 

cefepime: 

• Action: cefepime is a fourth-generation cephalosporin antibiotic that disrupts the bacterial cell wall synthesis. It does this by binding to penicillin-binding proteins (PBPs), enzymes involved in cell wall formation. This leads to cell wall damage and eventual bacterial cell death. 
• Spectrum: cefepime has a broad spectrum of activity against both Gram-negative and Gram-positive bacteria. It is often used to treat infections caused by Enterobacteriaceae and certain Gram-positive bacteria like Streptococcus pneumoniae. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Nephrotoxicity 

ototoxicity 

Neuro muscular disorders 

Rashes 

Pruritus 

Nausea 

Dizziness 

Vertigo 

Vaginitis 

Candiasis 

Vomiting 

Headache 

Hypotension 

Black Box Warning

Black Box Warning: 

There were no specific black box warnings associated with amikacin and cefepime. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: The combination of amikacin and cefepime should not be used in patients with a known hypersensitivity or allergy to either amikacin, cefepime, or any other components of these medications. Allergic reactions can be severe and life-threatening. 
• Renal Impairment: Both amikacin and Cefepime are primarily excreted by the kidneys. Therefore, caution is advised when using this combination in patients with significant renal impairment or kidney dysfunction. Dose adjustments may be necessary to prevent the accumulation of these drugs in the body. 
• Neurological Disorders: Cefepime, when used at high doses, has been associated with neurotoxicity, which can manifest as altered mental status, seizures, and encephalopathy. Therefore, the combination should be used cautiously in patients with pre-existing neurological disorders or conditions that may increase the risk of neurotoxicity. 
• Myasthenia Gravis: Cefepime can exacerbate symptoms of myasthenia gravis, a neuromuscular disorder. It should be used with caution in patients with myasthenia gravis.

Caution: 

• Nephrotoxicity: Both amikacin and Cefepime can be nephrotoxic, especially when used in high doses or for prolonged periods. Patients with pre-existing kidney dysfunction or those at risk of renal impairment should be closely monitored for changes in kidney function. Regular monitoring of serum creatinine levels and adjusting the dosage as necessary is essential. 
• Neurotoxicity: High doses of Cefepime have been associated with neurotoxicity, which can manifest as altered mental status, seizures, or encephalopathy. Caution should be used, especially in patients with underlying neurological conditions. Promptly report any signs of neurological dysfunction. 
• Drug Interactions: Check for potential drug interactions when using this combination with other medications. For example, certain diuretics (e.g., furosemide) can increase the risk of nephrotoxicity when used concomitantly with amikacin. Your healthcare provider will consider these interactions and adjust dosages as needed. 
• Pregnancy and Lactation: The safety of this combination during pregnancy and breastfeeding is not well-established. It should be used during pregnancy only if the potential benefits outweigh the risks, and breastfeeding should be avoided during treatment.

Comorbidities: 

• Hepatic Impairment: Patients with liver disease or impaired liver function may have difficulty metabolizing drugs like Cefepime. Dosing adjustments may be required in individuals with hepatic impairment. 
• Diabetes: Patients with diabetes may be at a higher risk of infections, and their blood sugar levels should be closely monitored when receiving antibiotics. 
• Immunocompromised Patients: Individuals with weakened immune systems, such as those with HIV/AIDS or undergoing chemotherapy, may be more susceptible to severe bacterial infections. The use of antibiotics like amikacin and Cefepime in these patients should be guided by infectious disease specialists and tailored to their specific needs. 
• Geriatric Patients: Elderly patients may have multiple comorbidities and age-related changes in renal and hepatic function, which can affect the pharmacokinetics of these medications. Dosing adjustments and close monitoring are often necessary in this population. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category: not assigned 

Lactation: excreted into human milk: unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• <b>Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

The combination of amikacin and Cefepime brings together two powerful antibiotics with distinct mechanisms of action to a broad spectrum of bacterial infections. amikacin belongs to the aminoglycoside class and inhibits bacterial protein synthesis, leading to impaired protein production and bacterial cell death.

Cefepime is a cephalosporin antibiotic that interferes with bacterial cell wall synthesis by targeting penicillin-binding proteins. Together, these antibiotics exhibit synergy against a wide range of Gram-negative and some Gram-positive bacteria. Their combined action provides a dual attack strategy, making this combination valuable in treating severe and complex infections, including those caused by multidrug-resistant pathogens.  

Pharmacodynamics: 

• amikacin: amikacin is an aminoglycoside antibiotic with a concentration-dependent bactericidal effect. It exerts its action by irreversibly binding to the 30S ribosomal subunit of bacterial ribosomes, leading to misreading of mRNA and inhibition of protein synthesis. amikacin’s bactericidal activity is concentration-dependent, meaning that higher drug concentrations in the bloodstream result in more efficient bacterial killing. 
• Cefepime: Cefepime is a fourth-generation cephalosporin antibiotic with a time-dependent bactericidal effect. It acts by interfering cell wall synthesis. Cefepime binds to penicillin-binding proteins (PBPs) on the bacterial cell membrane, disrupting cell wall formation and leading to cell lysis. 

When combined, amikacin and Cefepime work synergistically to target a broad spectrum of bacteria, including both Gram-negative and some Gram-positive pathogens. This combination exploits amikacin’s concentration-dependent killing, ensuring rapid bacterial eradication, and Cefepime’s time-dependent killing, which helps maintain sustained antibacterial activity over time. The synergy between these two antibiotics is particularly valuable in treating severe infections where broad coverage and rapid bacterial clearance are crucial.  

Pharmacokinetics: 

Absorption: 

• amikacin: This aminoglycoside antibiotic is not well absorbed when taken orally, and it is typically administered via intravenous or intramuscular injection to achieve therapeutic levels in the bloodstream. 
• cefepime: Cefepime is available in both intravenous and intramuscular formulations, bypassing the need for oral absorption. It is rapidly absorbed after injection. 

Distribution: 

• amikacin: After administration, amikacin is distributed widely throughout the body, with good penetration into many tissues and body fluids, including the lungs, kidneys, and skin. 
• cefepime: cefepime also has good distribution into various tissues and body fluids. It can achieve therapeutic concentrations in tissues such as the respiratory tract, abdominal tissues, and skin. 

Metabolism: 

• amikacin: amikacin is not significantly metabolized in the body. It is primarily eliminated unchanged through renal excretion. 
• cefepime: cefepime undergoes minimal metabolism, primarily being eliminated unchanged in the urine. 

Excretion: 

• amikacin: amikacin is primarily eliminated through the kidneys by glomerular filtration. The drug gets excreted unchanged in the urine. 
• cefepime: cefepime is primarily excreted unchanged in the urine. Dose adjustments may be necessary in patients with impaired renal function to prevent drug accumulation and potential toxicity. 

Adminstartion

Administration: 

• Dosage: The specific dosage of amikacin and Cefepime in this combination will depend on the patient’s age, weight, renal function, and the type and severity of the infection being treated. It is essential to follow the prescribing physician’s orders and the recommended dosing regimen. 
• Infusion: The medications are typically given separately but can be mixed in the same IV bag if compatible. Always follow the manufacturer’s instructions and the hospital’s guidelines for IV admixture. 
• Renal Function: Since both amikacin and Cefepime are primarily excreted by the kidneys, it is crucial to monitor renal function regularly, especially in patients with compromised kidney function. 
• Duration: The duration of treatment with this combination will vary based on the infection being treated. Follow the prescribed treatment course, even if the patient’s symptoms improve before completing the entire course. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: amikacin and cefepime 

Pronounced: (uh-MIK-uh-sin-and-sef-uh-PEEM)  

Why do we use amikacin and cefepime? 

• Severe Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP): These infections often involve multidrug-resistant bacteria. The combination of amikacin and Cefepime may be used as part of empiric therapy until specific pathogens and their sensitivities are identified. 
• Complicated Urinary Tract Infections (cUTIs): In cases where cUTIs is caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria or other multidrug-resistant pathogens, this combination may be considered. 
• Febrile Neutropenia: In cancer patients undergoing chemotherapy or individuals with compromised immune systems, amikacin and cefepime can be used to treat febrile neutropenia when there is a high risk of bacterial infection.