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# Ceftazidime-avibactam
## Overview
Ceftazidime-avibactam is a combination antibiotic consisting of a third-generation cephalosporin (ceftazidime) and a beta-lactamase inhibitor (avibactam). It is active against many Gram-negative bacteria, including difficult-to-treat pathogens like *Pseudomonas aeruginosa* and carbapenem-resistant Enterobacterales (CRE).
## Primary Indications
* Complicated intra-abdominal infections (cIAI), in combination with metronidazole.
* Complicated urinary tract infections (cUTI), including pyelonephritis.
* Hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP).
* Includes treatment of infections caused by susceptible Gram-negative bacteria.
## Adult Dosing
**Complicated Intra-abdominal Infections (cIAI):**
2.5 grams (ceftazidime 2 g / avibactam 0.5 g) intravenously every 8 hours for 5-14 days. Always administer with metronidazole.
**Complicated Urinary Tract Infections (cUTI) and Hospital-acquired Pneumonia (HAP)/Ventilator-associated Pneumonia (VAP):**
2.5 grams (ceftazidime 2 g / avibactam 0.5 g) intravenously every 8 hours for 7-14 days.
Duration of therapy depends on the severity of infection, pathogen, and clinical response. For cIAI, consult local guidelines regarding the role of metronidazole.
## Pediatric Dosing
Established pediatric dosing varies by age and indication. Refer to specific pediatric guidelines or product labeling.
* **Children 3 months to < 18 years:** Dosing is weight-based and may be different for cUTI/HAP/VAP vs. cIAI (in combination with metronidazole). For example, for cUTI/HAP/VAP, dosing can range from 33.75 mg/kg (ceftazidime) / 6.75 mg/kg (avibactam) up to 100 mg/kg (ceftazidime) / 20 mg/kg (avibactam) administered intravenously every 8 hours. The maximum single dose should not exceed 2 g ceftazidime / 0.5 g avibactam.
## Dose Adjustments
**Renal Impairment:**
* **CrCl 30 to 50 mL/min:** 1.25 grams (ceftazidime 1 g / avibactam 0.25 g) intravenously every 8 hours.
* **CrCl < 30 mL/min:** 0.75 grams (ceftazidime 0.6 g / avibactam 0.15 g) intravenously every 12 hours.
* **Hemodialysis:** Dosing requires specific consideration based on dialysis schedule. Consult product information.
**Hepatic Impairment:** No dose adjustment is generally needed for mild to moderate hepatic impairment. Severe hepatic impairment data is limited.
## Contraindications
* Known severe hypersensitivity to ceftazidime, avibactam, other cephalosporins, penicillins, or any component of the formulation.
## Adverse Effects
* Nausea
* Vomiting
* Diarrhea
* Headache
* Increased liver enzymes (AST, ALT)
* Hypersensitivity reactions (rash, pruritus, anaphylaxis)
* Infusion-related reactions
* Clostridioides difficile-associated diarrhea
## Key Drug Interactions
* **Probenecid:** May increase serum concentrations of ceftazidime.
* **Oral contraceptives:** Cephalosporins may reduce the efficacy of oral contraceptives. Advise patients to use alternative or additional non-hormonal contraception.
## Monitoring
* Monitor for signs and symptoms of hypersensitivity reactions.
* Monitor for signs of C. difficile infection.
* Renal function (especially if CrCl is borderline or changing).
* Liver function tests.
* Clinical signs of infection and pathogen susceptibility.
## Clinical Pearls
* Ceftazidime-avibactam is administered via intravenous infusion. Reconstitution and dilution instructions are critical.
* Empiric therapy should be guided by local susceptibility patterns and resistance data.
* When treating cIAI, metronidazole must be administered concurrently due to its broad coverage against anaerobes, which are not covered by ceftazidime-avibactam.
* Resistance to ceftazidime-avibactam can emerge; appropriate diagnostic testing should be performed.
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**Disclaimer:** This information is intended for clinical decision support and does not replace professional medical judgment or the official prescribing information. Always verify current dosing, indications, contraindications, and safety warnings with the most recent product labeling and institutional protocols.
