Can ceftazidime and aztreonam (Azactam) be administered simultaneously?

Can Ceftazidime and Aztreonam Be Administered Simultaneously?

Yes, ceftazidime-avibactam and aztreonam can and should be administered simultaneously when treating metallo-β-lactamase (MBL)-producing organisms, as simultaneous administration demonstrates superior bacterial killing and resistance suppression compared to staggered administration. 1

Evidence for Simultaneous Administration

Compatibility Data

• Ceftazidime-avibactam is physically compatible with aztreonam when administered via Y-site infusion. 2
• Compatibility has been demonstrated at ceftazidime-avibactam concentrations of 8,25, and 50 mg/mL combined with aztreonam concentrations of 10 and 20 mg/mL. 2
• No particulate matter, color changes, turbidity, or pH changes were observed over 12 hours in both simulated and actual Y-site administration studies. 2
• The FDA label for aztreonam does not list ceftazidime as an incompatible agent, though it does specify that nafcillin, cephradine, and metronidazole are incompatible. 3

Pharmacokinetic Interactions

• Coadministration of ceftazidime-avibactam with aztreonam reduces total aztreonam clearance by only 16%, which is clinically insignificant. 4
• Aztreonam has negligible effect on ceftazidime clearance when administered together. 4
• Ceftazidime does not affect the in vitro antimicrobial activity of aztreonam-avibactam against MBL-producing Enterobacterales—MICs remain within one 2-fold dilution regardless of ceftazidime concentration. 5

Clinical Superiority of Simultaneous vs. Staggered Administration

• Hollow-fiber infection model studies demonstrate that simultaneous administration produces superior bacterial killing compared to staggered administration (ceftazidime-avibactam followed by aztreonam). 1
• Simultaneous administration with aztreonam 8 g/day (either as continuous infusion or 2-hour infusions every 6 hours) combined with ceftazidime-avibactam resulted in complete bacterial eradication and resistance suppression over 7 days against NDM-1-producing organisms. 1

Recommended Administration Protocol

For MBL-Producing Organisms (NDM, VIM, IMP)

• Administer ceftazidime-avibactam 2.5 g IV every 8 hours as a 3-hour infusion PLUS aztreonam 2 g IV every 6 hours simultaneously. 6, 1
• The 3-hour prolonged infusion of ceftazidime-avibactam is associated with improved 30-day survival. 6
• This combination demonstrates synergistic activity in 90% of MBL-producing strains. 6

Y-Site Administration Technique

• When using a Y-type administration set, flush the common delivery tube before and after aztreonam delivery with a compatible infusion solution. 3
• Do not deliver both drugs through the same line if they are not pharmaceutically compatible with the carrier solution. 3
• Complete any aztreonam infusion within 20-60 minutes. 3

Clinical Outcomes Data

• The ceftazidime-avibactam plus aztreonam combination achieves significantly lower 30-day mortality (HR: 0.37,95% CI 0.13-0.74) and lower clinical failure rates compared to other antimicrobial therapies for MBL-producing CRE. 7
• Case reports demonstrate clinical success with this combination even in critically ill patients with carbapenemase-producing Klebsiella pneumoniae bacteremia. 8

Important Safety Considerations

• Coadministration of ceftazidime-avibactam with aztreonam does not exacerbate ALT/AST elevations relative to aztreonam alone. 4
• However, continuous infusion aztreonam should be used with caution due to observed severe ALT/AST elevations in phase 1 studies (though all were asymptomatic and resolved after cessation). 4
• All ALT/AST elevations in combination therapy studies were asymptomatic with no other signs of liver injury and resolved without sequelae. 4

Allergy Cross-Reactivity Caveat

• Avoid aztreonam in patients with suspected immediate-type or delayed-type allergy to ceftazidime or cefiderocol (within 1 year of reaction), as these agents share similar side chains that may cause cross-reactivity. 9
• Aztreonam can be safely used in patients with allergies to other cephalosporins (excluding ceftazidime/cefiderocol) due to minimal cross-reactivity. 9