Cefepime

# Cefepime ## Overview - **Classification**: Fourth-generation cephalosporin antibiotic. - **Mechanism**: Inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to bacterial lysis. ## Primary Indications 1. **Severe Infections**: Including complicated intra-abdominal infections, urinary tract infections (cUTI). 2. **Febrile Neutropenia**: Empiric monotherapy or in combination. 3. **Nosocomial Pneumonia**: Including severe cases and ventilator-associated pneumonia (VAP). 4. **Bacterial Meningitis**: In susceptible pathogens. ## Adult Dosing ### Standard Dosing **Severe Infections (e.g., cUTI, mild-moderate nosocomial pneumonia)** - **Dose**: **1 g** - **Frequency**: Every **8-12 hours** - **Route**: Intravenous (IV) - **Maximum Dose**: **2 g** per dose **Severe Infections (e.g., severe nosocomial pneumonia, empiric febrile neutropenia, complicated intra-abdominal infections)** - **Dose**: **2 g** - **Frequency**: Every **8 hours** - **Route**: Intravenous (IV) - **Maximum Dose**: **2 g** per dose (**6 g/day**) - **Special Considerations**: Extended or continuous infusions may be used in select cases for resistant pathogens or critically ill patients (off-label). **Bacterial Meningitis** - **Dose**: **2 g** - **Frequency**: Every **8 hours** - **Route**: Intravenous (IV) - **Maximum Dose**: **2 g** per dose (**6 g/day**) ### Dose Adjustments - **Renal Impairment**: Requires significant dose reduction to prevent neurotoxicity. - CrCl > 60 mL/min: Standard dosing - CrCl 30-60 mL/min: **2 g** q24h or **1 g** q12h (for 2g q8h original dose) - CrCl 11-29 mL/min: **1 g** q24h or **0.5 g** q12h (for 2g q8h original dose) - CrCl < 11 mL/min: **0.5 g** q24h - Hemodialysis: Administer a loading dose, then **1 g** after each dialysis session. - Peritoneal Dialysis: **1 g** every **48 hours**. - **Hepatic Impairment**: No specific dose adjustment needed. - **Elderly Patients**: Adjust dose based on renal function, which commonly declines with age. Start with lower end of dosing range. ## Pediatric Dosing ### Neonates (0-28 days) - **Indication**: Serious infections (e.g., suspected sepsis, meningitis) - **Dose**: **30 mg/kg** (for 0-7 days, <1200g); **50 mg/kg** (>7 days or >1200g) - **Frequency**: Every **12 hours** (for 0-7 days); Every **8 hours** (>7 days) - **Route**: Intravenous (IV) - **Maximum**: **50 mg/kg/dose** - **Special Notes**: Consider longer dosing intervals in premature infants due to immature renal function. ### Infants (1-12 months) - **Indication**: Serious infections (e.g., sepsis, meningitis, febrile neutropenia) - **Dose**: **50 mg/kg** - **Frequency**: Every **8 hours** (for severe infections, meningitis, febrile neutropenia) or Every **12 hours** (for moderate infections like UTI) - **Route**: Intravenous (IV) - **Maximum**: **2 g/dose** ### Children (1-12 years) - **Indication**: Serious infections (e.g., sepsis, meningitis, febrile neutropenia) - **Dose**: **50 mg/kg** - **Frequency**: Every **8 hours** (for severe infections, meningitis, febrile neutropenia) or Every **12 hours** (for moderate infections like UTI) - **Route**: Intravenous (IV) - **Maximum**: **2 g/dose** (do not exceed adult maximum) ### Adolescents (13-18 years) - **Indication**: Serious infections - **Dose**: Generally follows **adult dosing guidelines** based on indication. - **Route**: Intravenous (IV) - **Maximum**: **2 g/dose** (**6 g/day**) ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to cefepime, other cephalosporins, penicillins, or other beta-lactam antibiotics. - **Relative**: History of severe immediate hypersensitivity to other beta-lactam antibiotics (e.g., anaphylaxis). ### Common Adverse Effects - **Common (1-10%)**: Diarrhea, nausea, vomiting, rash, fever. - **Common (1-10%)**: Injection site reactions (phlebitis), positive Coombs test (without hemolysis). - **Serious but Rare**: Neurotoxicity (encephalopathy, seizures, confusion), especially with renal dysfunction. - **Serious but Rare**: Clostridioides difficile-associated diarrhea (CDAD), severe hypersensitivity reactions (anaphylaxis), agranulocytosis. ### Key Drug Interactions - **Aminoglycosides (e.g., Gentamicin)**: Increased risk of nephrotoxicity. Monitor renal function closely. - **Loop Diuretics (e.g., Furosemide)**: May increase cefepime concentrations. Monitor for toxicity. - **Live Bacterial Vaccines (e.g., BCG, Typhoid oral)**: Cefepime may reduce vaccine efficacy. - **Oral Anticoagulants (e.g., Warfarin)**: May enhance anticoagulant effect. Monitor INR. ## Monitoring & Follow-up - **Before Treatment**: Obtain culture and susceptibility results if possible. Assess renal function (SCr, CrCl). - **During Treatment**: Monitor renal function daily in patients with unstable renal function or q2-3 days otherwise. - **During Treatment**: Monitor for signs of neurotoxicity (altered mental status, seizures), especially in renal impairment. - **Clinical Signs**: Assess for resolution of infection signs/symptoms, signs of C. difficile infection (diarrhea). ## Clinical Pearls - 💡 **Nephrotoxicity Risk**: Always calculate and adjust dose for renal function; high risk of neurotoxicity if overdosed in kidney impairment. - 💡 **Neurotoxicity**: If unexplained altered mental status, myoclonus, or seizures occur, consider cefepime toxicity, especially if renal function is impaired. - 💡 **Cross-reactivity**: Generally low cross-reactivity with penicillin allergy, but caution with immediate-type hypersensitivity. - 💡 **Pseudomonas coverage**: Cefepime has excellent activity against _Pseudomonas aeruginosa_ and many Gram-negative rods. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.