What is the recommended use and dosage of Avibactam (ceftazidime/avibactam) for treating infections?

Ceftazidime-Avibactam (Avibactam) Treatment Guidelines

Standard Dosing and Administration

The recommended dosage of ceftazidime-avibactam is 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) administered intravenously every 8 hours over 2 hours in adults with normal renal function (CrCl >50 mL/min). 1

Approved Indications and Treatment Durations

Complicated Intra-Abdominal Infections (cIAI)

• Ceftazidime-avibactam must be given concurrently with metronidazole 500 mg IV every 6-8 hours for cIAI coverage of anaerobes. 2, 3, 1
• Treatment duration is 5-14 days, with the Infectious Diseases Society of America recommending 5-7 days when adequate source control is achieved. 3, 4, 1
• The combination targets Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii complex, and Pseudomonas aeruginosa. 1

Complicated Urinary Tract Infections (cUTI) Including Pyelonephritis

• Treatment duration is 7-14 days for cUTI, with European guidelines supporting 5-7 days for uncomplicated cases. 3, 4, 1
• Ceftazidime-avibactam demonstrated 70.4% microbiologic success rates comparable to imipenem-cilastatin (71.4%) in Phase II trials. 5, 6
• The agent covers the same gram-negative pathogens as listed for cIAI. 1

Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (HABP/VABP)

• Treatment duration is 7-14 days for HABP/VABP. 3, 1
• Coverage includes Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae. 1

Bloodstream Infections

• The Infectious Diseases Society of America recommends 7-14 days of treatment for bloodstream infections caused by susceptible organisms. 4

Carbapenem-Resistant Organisms

KPC-Producing and OXA-48-Producing Enterobacterales

• Ceftazidime-avibactam is the preferred agent for carbapenem-resistant Enterobacterales (CRE) infections, particularly those producing KPC or OXA-48 enzymes, at the standard dose of 2.5 g IV every 8 hours. 2
• The Infectious Diseases Society of America and Centers for Disease Control and Prevention endorse ceftazidime-avibactam as first-line therapy for CRE infections. 2, 4

Metallo-Beta-Lactamase (MBL) Producers

• Ceftazidime-avibactam is NOT active against MBL-producing organisms; aztreonam must be used instead, often in combination with ceftazidime-avibactam for synergy. 2

Difficult-to-Treat Pseudomonas aeruginosa

• Ceftazidime-avibactam is effective against multidrug-resistant P. aeruginosa at 2.5 g IV every 8 hours. 2

Pediatric Dosing

Weight-Based Dosing by Age Group

• Children 2 to <18 years: 62.5 mg/kg (maximum 2.5 grams) IV every 8 hours over 2 hours. 1
• Children 6 months to <2 years: 62.5 mg/kg IV every 8 hours over 2 hours. 1
• Children 3 to <6 months: 50 mg/kg IV every 8 hours over 2 hours. 1
• Infants >28 days to <3 months: 37.5 mg/kg IV every 8 hours over 2 hours. 1
• Neonates ≤28 days with gestational age ≥31 weeks: 25 mg/kg IV every 8 hours over 2 hours. 1
• Treatment durations mirror adult recommendations: cIAI 5-14 days, cUTI 7-14 days, HABP/VABP 7-14 days. 1

Renal Dose Adjustments

• Dosage adjustments are mandatory for adults and pediatric patients ≥2 years with CrCl or eGFR ≤50 mL/min. 1
• Monitor renal function daily in patients with changing kidney function and adjust doses accordingly. 1
• The FDA label provides specific reduced dosing regimens based on creatinine clearance categories. 1

Critical Resistance Considerations

Emerging Resistance Patterns

• Resistance to ceftazidime-avibactam in KPC-producing organisms has been reported, particularly with prior ceftazidime-avibactam exposure, due to mutations in the blaKPC-3 gene. 2, 3
• The Centers for Disease Control and Prevention emphasizes careful monitoring and judicious use to prevent resistance development. 2

Combination Therapy for High-Risk Scenarios

• Consider combination therapy with ceftazidime-avibactam plus a carbapenem or colistin when treating KPC-3 producers due to potential resistance development. 2

Pharmacokinetic/Pharmacodynamic Optimization

• The 2-hour infusion over 8-hour dosing interval achieves optimal PK/PD targets: 50% free time above MIC for ceftazidime and free time above 1 mg/L for avibactam. 7
• Target attainment exceeds 95% against MICs ≤8 mg/L regardless of obesity, older age, augmented renal clearance, or infection severity. 7

Common Pitfalls to Avoid

• Never use ceftazidime-avibactam alone for cIAI—metronidazole is mandatory for anaerobic coverage. 3, 1
• Do not assume activity against MBL-producing organisms; verify carbapenemase type before use. 2
• Avoid empiric use without considering local resistance patterns and prior antibiotic exposure. 2, 3
• Remember to adjust for renal impairment to prevent toxicity and maintain efficacy. 1

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