Imipenem

# Imipenem ## Overview - **Classification**: Carbapenem antibiotic (combined with Cilastatin, a dehydropeptidase inhibitor) - **Mechanism**: Inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). Cilastatin prevents renal metabolism of imipenem, increasing its urinary concentration and reducing nephrotoxicity. ## Primary Indications 1. **Severe Bacterial Infections**: Broad-spectrum coverage for resistant or polymicrobial infections. 2. **Complicated Intra-abdominal Infections**: Including peritonitis and appendicitis with rupture. 3. **Lower Respiratory Tract Infections**: Such as severe pneumonia. 4. **Bacterial Septicemia**: Empiric or directed therapy for bloodstream infections. ## Adult Dosing ### Standard Dosing **Severe Bacterial Infections (e.g., complicated intra-abdominal, lower respiratory tract, septicemia)** - **Dose**: **500 mg** (imipenem equivalent) - **Frequency**: Every **6 hours** - **Route**: Intravenous (IV) infusion over 30-60 minutes - **Maximum Dose**: **4 grams/day** **Moderate Infections (e.g., less severe pneumonia, UTIs)** - **Dose**: **250 mg - 500 mg** (imipenem equivalent) - **Frequency**: Every **6 hours** - **Route**: Intravenous (IV) infusion over 30-60 minutes - **Maximum Dose**: **4 grams/day** ### Dose Adjustments - **Renal Impairment**: Dose must be reduced based on CrCl to prevent accumulation and seizure risk. - CrCl 30-69 mL/min: **250-500 mg Q8-12H** (Max 3 g/day) - CrCl 10-29 mL/min: **250-500 mg Q12H** (Max 2 g/day) - CrCl <10 mL/min (not on HD): **250 mg Q12H** (Max 1 g/day) - Hemodialysis: Administer dose after dialysis. **250-500 mg Q12H** (Max 1 g/day). - **Hepatic Impairment**: No specific dose adjustment necessary. - **Elderly Patients**: Dose adjust based on renal function, typically no other specific adjustments. ## Pediatric Dosing ### Neonates (0-28 days) - **Dose**: **25 mg/kg** (imipenem equivalent) - **Frequency**: Every **6 hours** - **Maximum**: Not to exceed **100 mg/kg/day** - **Special Notes**: Consider prolonged infusion times in very young neonates due to immature renal function. ### Infants (1-12 months) - **Dose**: **25 mg/kg** (imipenem equivalent) - **Frequency**: Every **6 hours** - **Maximum**: Not to exceed **100 mg/kg/day** or **2 grams/day**, whichever is lower. ### Children (1-12 years) - **Dose**: **15-25 mg/kg** (imipenem equivalent) - **Frequency**: Every **6 hours** - **Maximum**: Not to exceed **2 grams/day** for lower doses or **4 grams/day** for higher doses, or **60 mg/kg/day**, whichever is lower. Max single dose **1 gram**. ### Adolescents (13-18 years) - **Dose**: Typically follows **adult dosing** guidelines. - **Maximum**: **4 grams/day** (imipenem equivalent). ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to Imipenem, Cilastatin, or other carbapenems. - **Absolute**: Severe hypersensitivity reaction to other beta-lactam antibiotics (e.g., penicillin, cephalosporins). ### Common Adverse Effects - **Common (1-10%)**: Nausea, vomiting, diarrhea, rash, pruritus. - **Less Common (<1%)**: Eosinophilia, increased LFTs, phlebitis at infusion site. - **Serious but Rare**: **Seizures**, other CNS effects (confusion, myoclonus), pseudomembranous colitis (C. difficile), severe allergic reactions. ### Key Drug Interactions - **Valproic Acid**: Imipenem can significantly decrease valproic acid levels, leading to loss of seizure control. **Concomitant use is generally not recommended.** - **Ganciclovir**: Concomitant use with imipenem has been reported to cause generalized seizures. Avoid concomitant use if possible. - **Probenecid**: May increase imipenem levels. Not clinically relevant due to cilastatin. ## Monitoring & Follow-up - **Before Treatment**: Assess baseline renal function (BUN, creatinine) and liver function (AST, ALT). - **During Treatment**: Monitor renal function (BUN, creatinine) periodically, especially in patients with renal impairment. Monitor for CNS symptoms (seizures) and gastrointestinal disturbances. - **Clinical Signs**: Watch for signs of superinfection (e.g., C. difficile diarrhea), allergic reactions (rash, dyspnea), or CNS changes. ## Clinical Pearls - 💡 **Infusion Rate**: Infuse over **30-60 minutes** to reduce the risk of nausea, vomiting, and phlebitis. - 💡 **Seizure Risk**: Highest in patients with renal impairment, pre-existing CNS disorders (e.g., epilepsy, head injury), or if doses exceed recommendations. Always adjust for renal function. - 💡 **Broad Spectrum**: Imipenem has a very broad spectrum against Gram-positive, Gram-negative, and anaerobic bacteria. Reserve for severe or resistant infections to prevent resistance. - 💡 **Stability**: Reconstituted solution should be used promptly (e.g., within 4 hours at room temp, 24 hours refrigerated for NS). > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.