Ceftazidime Avibactam

# CEFTAZIDIME AVIBACTAM ## Overview - **Classification**: Cephalosporin (3rd gen) + Beta-lactamase inhibitor combination - **Mechanism**: Ceftazidime inhibits bacterial cell wall synthesis. Avibactam restores ceftazidime activity against beta-lactamase producing bacteria. ## Primary Indications 1. **Complicated Intra-abdominal Infections (cIAI)** - Used in combination with metronidazole. 2. **Complicated Urinary Tract Infections (cUTI)** - Including pyelonephritis. 3. **Hospital-acquired Bacterial Pneumonia (HABP)** and **Ventilator-associated Bacterial Pneumonia (VABP)** ## Adult Dosing ### Standard Dosing **cIAI, cUTI (incl. pyelonephritis), HABP/VABP** - **Dose**: **2.5 grams** (ceftazidime 2 grams / avibactam 0.5 grams) - **Frequency**: Every **8 hours** - **Route**: Intravenous (IV) infusion over **2 hours** - **Duration**: 7-14 days depending on infection type and response. ### Dose Adjustments - **Renal Impairment**: - **CrCl > 50 mL/min**: No dose adjustment. - **CrCl 31-50 mL/min**: **1.25 grams** IV q8h. - **CrCl 16-30 mL/min**: **0.625 grams** IV q8h. - **CrCl 6-15 mL/min**: **0.625 grams** IV q12h. - **ESRD (CrCl < 5 mL/min) on HD**: **0.625 grams** IV daily on non-dialysis days; on dialysis days, administer post-dialysis. - **Hepatic Impairment**: No dose adjustment needed. - **Elderly Patients**: Adjust based on renal function, not age alone. ## Pediatric Dosing ### Neonates (0-28 days) - **Use with caution**: Limited data; generally not recommended unless no other options. - **Consider consultation**: With infectious disease or pediatric specialist. ### Infants (1 to <3 months) - **cIAI, cUTI (incl. pyelonephritis)**: - **Dose**: **50 mg/kg** (ceftazidime component) / **12.5 mg/kg** (avibactam component) - **Frequency**: Every **8 hours** - **Maximum**: **2.5 grams** IV q8h. ### Children (3 months to <18 years) - **cIAI, cUTI (incl. pyelonephritis)**: - **Dose**: **50 mg/kg** (ceftazidime component) / **12.5 mg/kg** (avibactam component) - **Frequency**: Every **8 hours** - **Maximum**: **2.5 grams** IV q8h. - **HABP/VABP (≥12 years, weighing ≥30 kg)**: Use adult dosing. ### Adolescents (13-18 years) - **Weight ≥30 kg**: Use adult dosing of **2.5 grams** IV q8h. - **Weight <30 kg**: Use pediatric dosing of **50 mg/kg** (ceftazidime) / **12.5 mg/kg** (avibactam) q8h. - **Maximum**: **2.5 grams** IV q8h. ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to ceftazidime, avibactam, or other beta-lactam antibacterial drugs (e.g., penicillins, other cephalosporins). - **Relative**: History of severe hypersensitivity to other beta-lactams. ### Common Adverse Effects - **Common (1-10%)**: Nausea, vomiting, diarrhea, abdominal pain, headache, fever. - **Less Common (1-5%)**: Phlebitis at infusion site, rash, increased LFTs. - **Serious but Rare**: Anaphylaxis, Clostridioides difficile-associated diarrhea (CDAD), seizures (especially in renal impairment), neutropenia, agranulocytosis. ### Key Drug Interactions - **Probenecid**: May increase ceftazidime/avibactam concentrations; avoidance or close monitoring. - **Aminoglycosides**: No known direct interaction, but monitor renal function if co-prescribed due to individual nephrotoxicity risk. ## Monitoring & Follow-up - **Before Treatment**: Culture and susceptibility testing (when feasible), baseline renal function (SCr, CrCl). - **During Treatment**: - Renal function (SCr) daily or every 2-3 days, especially in renally impaired patients or on concomitant nephrotoxic drugs. - Signs/symptoms of anaphylaxis, CDAD, seizures. - Clinical response to therapy (e.g., fever, WBC, resolution of infection). - **Clinical Signs**: Monitor for rash, severe diarrhea, or neurological changes. ## Clinical Pearls - 💡 **Infusion Time**: Administer over **2 hours** to reduce risk of infusion reactions and ensure optimal drug exposure. - 💡 **Renal Adjustment is Crucial**: Significant dose adjustments are required for renal impairment to prevent toxicity (e.g., seizures). - 💡 **Combination Therapy**: For cIAI, always use in combination with metronidazole for anaerobic coverage. - 💡 **Spectrum**: Active against many Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae (CRE) and some P. aeruginosa. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.