What is the recommended dosage of Cefepime (Cefepime) for a patient with a bacterial infection and normal renal function, considering age, weight, and potential allergy to cephalosporins or penicillins?

Cefepime Dosage for Bacterial Infections with Normal Renal Function

For adults with normal renal function (CrCl >60 mL/min) and bacterial infections, administer cefepime 1-2 g IV every 8-12 hours, with the specific dose and interval determined by infection severity and pathogen susceptibility. 1

Standard Dosing by Infection Type

Moderate to Severe Pneumonia

• 1-2 g IV every 8-12 hours for 10 days 1
• For Pseudomonas aeruginosa specifically: 2 g IV every 8 hours 1
• Critically ill patients with severe pneumonia may require 2 g IV every 8 hours to achieve optimal pharmacodynamic targets 2

Urinary Tract Infections

• Mild to moderate (uncomplicated or complicated): 0.5-1 g IV every 12 hours for 7-10 days 1
• Severe (uncomplicated or complicated): 2 g IV every 12 hours for 10 days 1

Skin and Skin Structure Infections

• Moderate to severe uncomplicated infections: 2 g IV every 12 hours for 10 days 1

Complicated Intra-abdominal Infections

• 2 g IV every 8-12 hours for 7-10 days (must be combined with metronidazole for anaerobic coverage) 1

Febrile Neutropenia

• 2 g IV every 8 hours for 7 days or until resolution of neutropenia 1

Nosocomial/Healthcare-Associated Infections

• 2 g IV every 8 hours for critically ill patients with healthcare-associated infections 2
• For nosocomial endocarditis (early prosthetic valve ≤1 year after surgery): 100-150 mg/kg/day divided every 8-12 hours, up to 6 g/day 3

Pediatric Dosing (2 months to 16 years)

• Standard dose: 50 mg/kg IV every 12 hours (maximum 2 g per dose) 1
• For febrile neutropenia: 50 mg/kg IV every 8 hours (maximum 2 g per dose) 1
• For Pseudomonas infections: 50 mg/kg IV every 8 hours (maximum 2 g per dose) 3
• Neonates with gestational age <36 weeks: 30 mg/kg IV every 12 hours 3
• Neonates with gestational age ≥36 weeks: 50 mg/kg IV every 12 hours 3

Administration Considerations

Standard Infusion

• Administer IV over approximately 30 minutes 1
• This is appropriate for most infections with susceptible organisms (MIC ≤4 mg/L) 4

Extended Infusion Strategy

• For severe infections with high-MIC organisms (MIC ≥4 mg/L), consider extended infusions over 3-4 hours 2
• Extended infusions improve time above MIC, particularly important for Pseudomonas infections 2
• A loading dose can be given as rapid bolus initially, followed by extended infusions for subsequent doses 2

Critical Considerations for Optimal Efficacy

Critically Ill Patients

• Standard doses may be inadequate in ICU patients due to increased clearance and volume of distribution 2
• Studies show 37-44% of ICU patients fail to achieve therapeutic targets with standard dosing 2
• Consider 2 g IV every 8 hours for critically ill patients, even with normal renal function 2
• For infections with elevated MICs, doses exceeding 4 g daily may be required 2

Pharmacodynamic Targets

• Optimal efficacy requires free drug concentrations above the pathogen MIC for the entire dosing interval (100% T>MIC) in severe infections 2
• For pathogens with MIC ≤4 mg/L, standard dosing achieves adequate coverage in 100% of patients 4
• For pathogens with MIC ≥8 mg/L, only 45-65% of patients achieve adequate coverage with standard dosing 4

Contraindications and Allergy Considerations

Absolute Contraindication

• Prior immediate hypersensitivity reactions to cefepime, other cephalosporins, penicillins, or beta-lactam antibacterials 1

Cross-Reactivity Risk

• Cross-hypersensitivity among beta-lactam antibacterials may occur in up to 10% of patients with penicillin allergy 1
• If allergic reaction occurs during cefepime therapy, discontinue immediately 1

Common Pitfalls and Safety Monitoring

Neurotoxicity Risk

• May occur especially in patients with unrecognized renal impairment given unadjusted doses 1
• Symptoms include confusion, encephalopathy, myoclonus, and seizures 2
• Risk increases when trough concentrations exceed 8× MIC 2
• Two patients (10%) in one ICU study developed non-convulsive epilepsy symptoms (confusion, muscle jerks) with trough levels of 20-30 mg/L despite dose adjustment 4
• If neurotoxicity occurs, discontinue cefepime immediately 1

Therapeutic Drug Monitoring

• Consider TDM in critically ill patients, especially those with fluctuating renal function 2
• Plasma levels vary greatly between individuals (2-3 fold at peak, up to 40-fold at trough) 4
• Prompt monitoring should be considered when treating pathogens with MIC >4 mg/L or in patients with CrCl <50 mL/min 4

Most Common Adverse Reactions (≥1%)

• Local reactions, positive Coombs' test, decreased phosphorus, increased ALT/AST, increased PT/PTT, and rash 1
• At highest doses (2 g every 8 hours): rash, diarrhea, nausea, vomiting, pruritus, fever, and headache 1

Drug Interactions

• Aminoglycosides: increased potential for nephrotoxicity and ototoxicity 1
• Potent diuretics (e.g., furosemide): nephrotoxicity has been reported with other cephalosporins 1

Clostridioides difficile Risk

• Evaluate for CDAD if diarrhea develops during or after treatment 1