Administration of Ceftazidime-Avibactam and Aztreonam in Septicemia

Standard Dosing and Combination Therapy

The Infectious Diseases Society of America recommends administering ceftazidime-avibactam 2,500 mg (2,000 mg ceftazidime + 500 mg avibactam) as a 2-hour infusion every 8 hours, and if metallo-β-lactamase-producing organisms are suspected or confirmed, add aztreonam 2 grams every 8 hours as a separate infusion 1
Extended infusions (over several hours) increase the time above MIC and may be more effective than standard 30-minute infusions, especially for relatively resistant organisms in critically ill septic patients 2
The combination of ceftazidime-avibactam and aztreonam shows good in vitro synergy because aztreonam is not hydrolyzed by metallo-β-lactamases, while avibactam protects aztreonam from other β-lactamases 3
The combination is associated with significantly lower 30-day mortality (HR 0.37, 95% CI 0.13-0.74) compared to other active antimicrobial agents in bloodstream infections caused by MBL-producing organisms 3, 4

The Society of Critical Care Medicine recommends administering the first dose as soon as possible after sepsis recognition, ideally within the first hour, as delays in appropriate antibiotic therapy significantly increase mortality 2
Obtain blood cultures before initiating antibiotics 2
De-escalate from combination therapy to monotherapy within the first few days if clinical improvement occurs and susceptibility testing shows the organism is susceptible to ceftazidime-avibactam alone 1, 2
Ensure adequate fluid resuscitation (at least 30 mL/kg crystalloid) targeting MAP ≥65 mmHg before and during antibiotic therapy, as volume depletion contributes to sepsis-associated organ dysfunction 5

Do not use reduced doses in critically ill patients with normal renal function, as augmented renal clearance in early sepsis can lead to subtherapeutic levels 2
Do not use ceftazidime-avibactam alone for confirmed MBL-producing organisms, as this leads to treatment failure and increased mortality 1, 3
Prolonged infusion (3 hours) of ceftazidime-avibactam is independently associated with improved 30-day survival 4
Avoid concurrent nephrotoxins when possible, as each additional nephrotoxic agent increases acute kidney injury odds by 53% 2