Compatibility of Ceftazidime-Avibactam and Aztreonam with Stimulan
Yes, ceftazidime-avibactam and aztreonam can be used intravenously in patients who have Stimulan antibiotic-loaded bone cement implanted, as there is no contraindication to systemic administration of these antibiotics in the presence of antibiotic-impregnated cement.
Key Considerations
Intravenous Compatibility
- Ceftazidime-avibactam and aztreonam are fully compatible for simultaneous intravenous administration, with no evidence of incompatibility when mixed via Y-site at clinically relevant concentrations (ceftazidime-avibactam 8-50 mg/mL with aztreonam 10-20 mg/mL) 1
- The combination remains stable for at least 12 hours after mixing with no particulate matter, color changes, turbidity, or pH alterations 1
Clinical Use with Bone Cement
- Stimulan is a calcium sulfate-based antibiotic delivery system used for local antibiotic delivery in orthopedic infections
- There is no pharmacological interaction between systemically administered ceftazidime-avibactam/aztreonam and locally delivered antibiotics from bone cement - they work through different mechanisms (systemic vs. local tissue concentrations)
- The combination therapy is specifically indicated for severe infections including osteomyelitis caused by metallo-β-lactamase-producing organisms, where Stimulan might be used 2, 3
Clinical Efficacy Evidence
- The ceftazidime-avibactam plus aztreonam combination demonstrates significantly lower 30-day mortality (19.2% vs 44%) compared to other treatment options for MBL-producing Enterobacterales infections 4, 5
- This combination is recommended by ESCMID guidelines for severe CRE infections carrying metallo-β-lactamases 4, 3
Important Caveats
- Ensure the causative organism is an MBL-producer (NDM, VIM, IMP) before using this combination, as it is ineffective against non-MBL resistance mechanisms 3, 6
- The combination works because aztreonam is not hydrolyzed by metallo-β-lactamases, while avibactam protects aztreonam from ESBLs and AmpC enzymes commonly co-produced by these organisms 3
- Monitor for ceftazidime-avibactam resistance development during treatment, though this occurs in only 3.8-10.4% of cases 4