What is the dose of ceftazidime and avibactam for an adult patient with a suspected or confirmed bacterial infection?

Ceftazidime-Avibactam Dosing for Adult Patients

Standard Adult Dosing

The recommended dose of ceftazidime-avibactam for adults with normal renal function (CrCl >50 mL/min) is 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) administered intravenously every 8 hours as a 2-hour infusion. 1

Infection-Specific Dosing and Duration

Complicated Intra-Abdominal Infections (cIAI):

• Dose: 2.5 g IV every 8 hours over 2 hours 2, 1
• Critical requirement: Must be given concurrently with metronidazole 500 mg IV every 6-8 hours for anaerobic coverage 3, 2, 1
• Duration: 5-14 days, individualized based on source control adequacy and clinical response 2, 1

Complicated Urinary Tract Infections (cUTI) including Pyelonephritis:

• Dose: 2.5 g IV every 8 hours over 2 hours 2, 1
• Duration: 7-14 days 2, 1

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

• Dose: 2.5 g IV every 8 hours over 2 hours 1
• Duration: 7-14 days 2, 1

Bloodstream Infections (including CRE-BSI):

• Dose: 2.5 g IV every 8 hours over 2 hours 2
• Duration: 7-14 days 2

Renal Dose Adjustments

Dosing must be adjusted based on creatinine clearance (CrCl) to prevent subtherapeutic levels and treatment failure. 1, 4 A recent study demonstrated that renal dose adjustment was independently associated with increased mortality (HR 4.47), highlighting the critical importance of appropriate dosing while balancing renal function 4.

Monitor CrCl at least daily in patients with changing renal function and adjust dosing accordingly 1. The FDA label provides specific dose reductions for CrCl 31-50 mL/min, 16-30 mL/min, 6-15 mL/min, and end-stage renal disease 1.

Special Considerations for Severe Infections

For critically ill patients with severe infections, particularly pneumonia or septic shock, consider extended or continuous infusion strategies. 5 Standard 2-hour infusions may be insufficient to achieve optimal pharmacodynamic targets (100% fT>MIC) in patients with:

• Augmented renal clearance 5
• Severe pneumonia requiring higher lung penetration 6, 7
• Infections with organisms at higher MIC values (≥8 μg/mL) 5

For these patients, extending the infusion to 3-4 hours or using continuous infusion at higher dosages may be necessary to achieve therapeutic targets 5. One case report demonstrated that 2.5 g every 8 hours over 2 hours achieved adequate concentrations in a critically ill patient on continuous venovenous hemodiafiltration with Pseudomonas aeruginosa pneumonia 6.

Carbapenem-Resistant Enterobacterales (CRE) Infections

For suspected or confirmed CRE infections, ceftazidime-avibactam 2.5 g IV every 8 hours is recommended as a treatment option. 3, 2 When treating complicated intra-abdominal infections due to CRE, add metronidazole 500 mg every 8 hours 3.

Resistance Considerations

Important caveat: Emergence of ceftazidime-avibactam resistance has been reported in KPC-producing organisms, particularly with prior exposure to the drug 3, 2. When treating KPC-3 producers, some guidelines suggest considering combination therapy with a carbapenem or colistin, though evidence remains limited 3.

Critical Pitfalls to Avoid

• Never omit metronidazole when treating intra-abdominal infections—ceftazidime-avibactam lacks anaerobic coverage 3, 2, 1
• Do not use standard dosing in renal impairment—this leads to drug accumulation and potential toxicity 1
• Conversely, do not over-reduce doses in patients with acute kidney injury from sepsis, as this independently predicts mortality 4
• Monitor for treatment failure in patients with augmented renal clearance or severe pneumonia, where standard dosing may be subtherapeutic 5, 7